The nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.

<h4>Background</h4>The nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hyp...

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Autores principales: Lina Sabra-Makke, Cécile Tourrel-Cuzin, Raphaël G P Denis, Marthe Moldes, Jean-Paul Pégorier, Serge Luquet, Mireille Vasseur-Cognet, Pascale Bossard
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spelling oai:doaj.org-article:768df65102ba426b88a47dceafbd7b2f2021-11-18T07:03:10ZThe nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.1932-620310.1371/journal.pone.0013464https://doaj.org/article/768df65102ba426b88a47dceafbd7b2f2010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20976162/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hypothalamus compared to peripheral tissues.<h4>Methodology/principal findings</h4>Using hyperinsulinemic-euglycemic clamps and insulinopenic mice, we show that insulin upregulates its expression in the hypothalamus. Immunofluorescence studies demonstrate that COUP-TFII gene expression is restricted to a subpopulation of ventromedial hypothalamic neurons expressing the melanocortin receptor. In GT1-7 hypothalamic cells, the MC4-R agonist MTII leads to a dose dependant increase of COUP-TFII gene expression secondarily to a local increase in cAMP concentrations. Transfection experiments, using a COUP-TFII promoter containing a functional cAMP responsive element, suggest a direct transcriptional activation by cAMP. Finally, we show that the fed state or intracerebroventricular injections of MTII in mice induce an increased hypothalamic COUP-TFII expression associated with a decreased hepatic and pancreatic COUP-TFII expression.<h4>Conclusions/significance</h4>These observations strongly suggest that hypothalamic COUP-TFII gene expression could be a central integrator of insulin and melanocortin signaling pathway within the ventromedial hypothalamus. COUP-TFII could play a crucial role in brain integration of circulating signal of hunger and satiety involved in energy balance regulation.Lina Sabra-MakkeCécile Tourrel-CuzinRaphaël G P DenisMarthe MoldesJean-Paul PégorierSerge LuquetMireille Vasseur-CognetPascale BossardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 10, p e13464 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lina Sabra-Makke
Cécile Tourrel-Cuzin
Raphaël G P Denis
Marthe Moldes
Jean-Paul Pégorier
Serge Luquet
Mireille Vasseur-Cognet
Pascale Bossard
The nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.
description <h4>Background</h4>The nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hypothalamus compared to peripheral tissues.<h4>Methodology/principal findings</h4>Using hyperinsulinemic-euglycemic clamps and insulinopenic mice, we show that insulin upregulates its expression in the hypothalamus. Immunofluorescence studies demonstrate that COUP-TFII gene expression is restricted to a subpopulation of ventromedial hypothalamic neurons expressing the melanocortin receptor. In GT1-7 hypothalamic cells, the MC4-R agonist MTII leads to a dose dependant increase of COUP-TFII gene expression secondarily to a local increase in cAMP concentrations. Transfection experiments, using a COUP-TFII promoter containing a functional cAMP responsive element, suggest a direct transcriptional activation by cAMP. Finally, we show that the fed state or intracerebroventricular injections of MTII in mice induce an increased hypothalamic COUP-TFII expression associated with a decreased hepatic and pancreatic COUP-TFII expression.<h4>Conclusions/significance</h4>These observations strongly suggest that hypothalamic COUP-TFII gene expression could be a central integrator of insulin and melanocortin signaling pathway within the ventromedial hypothalamus. COUP-TFII could play a crucial role in brain integration of circulating signal of hunger and satiety involved in energy balance regulation.
format article
author Lina Sabra-Makke
Cécile Tourrel-Cuzin
Raphaël G P Denis
Marthe Moldes
Jean-Paul Pégorier
Serge Luquet
Mireille Vasseur-Cognet
Pascale Bossard
author_facet Lina Sabra-Makke
Cécile Tourrel-Cuzin
Raphaël G P Denis
Marthe Moldes
Jean-Paul Pégorier
Serge Luquet
Mireille Vasseur-Cognet
Pascale Bossard
author_sort Lina Sabra-Makke
title The nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.
title_short The nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.
title_full The nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.
title_fullStr The nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.
title_full_unstemmed The nutritional induction of COUP-TFII gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.
title_sort nutritional induction of coup-tfii gene expression in ventromedial hypothalamic neurons is mediated by the melanocortin pathway.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/768df65102ba426b88a47dceafbd7b2f
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